Novel POLR1C mutation in RNA polymerase III-related leukodystrophy with severe myoclonus and dystonia.
Mol Genet Genomic Med
; 7(9): e914, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-31368241
ABSTRACT
INTRODUCTION:
RNA polymerase III (Pol III)-related leukodystrophies are a group of autosomal recessive neurodegenerative disorders caused by mutations in POLR3A and POLR3B. Recently a recessive mutation in POLR1C causative of Pol III-related leukodystrophies was identified.METHODS:
We report the case of a Tunisian girl of 14 years of age who was referred to our department for evaluation of progressive ataxia that began at the age of 5. Genetic diagnosis was performed by NGS and Sanger analysis. In silico predictions were performed using SIFT, PolyPhen-2, and Mutation Taster.RESULTS:
Neurological examination showed cerebellar and tetrapyramidal syndrome, mixed movement disorders with generalized dystonia and severe myoclonus leading to death at 25 years. Brain MRI scans showed diffuse hypomyelination associated with cerebellar atrophy. It also showed bilateral T2 hypointensity of the ventrolateral thalamus, part of the posterior limb of the internal capsule, the substantia nigra and the subthalamic nucleus. Next generation sequencing leukodystrophy panel including POLR3A and POLR3B was negative. Sanger sequencing of the coding regions of POLR1C revealed a novel homozygous mutation.CONCLUSION:
The clinical and imaging findings of patients with POLR1C hypomyelinating leukodystrophy are reviewed. Interestingly, severe myoclonic dystonia and T2 hypointensity of the substantia nigra and the subthalamic nucleus are not reported yet and could be helpful for the diagnosis of POLR1C hypomyelinating leukodystrophy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Polimerasa III
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ARN Polimerasas Dirigidas por ADN
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Sustancia Negra
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Imagen por Resonancia Magnética
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Núcleo Subtalámico
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Encefalopatías Metabólicas Innatas
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Trastornos Distónicos
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Female
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Humans
Idioma:
En
Revista:
Mol Genet Genomic Med
Año:
2019
Tipo del documento:
Article
País de afiliación:
Túnez